Elsevier

The Lancet

Volume 366, Issue 9490, 17–23 September 2005, Pages 985-990
The Lancet

Articles
Long-term efficacy of early versus delayed radiotherapy for low-grade astrocytoma and oligodendroglioma in adults: the EORTC 22845 randomised trial

https://doi.org/10.1016/S0140-6736(05)67070-5Get rights and content

Summary

Background

Postoperative policies of “wait-and-see” and radiotherapy for low-grade glioma are poorly defined. A trial in the mid 1980s established the radiation dose. In 1986 the EORTC Radiotherapy and Brain Tumor Groups initiated a prospective trial to compare early radiotherapy with delayed radiotherapy. An interim analysis has been reported. We now present the long-term results.

Methods

After surgery, patients from 24 centres across Europe were randomly assigned to either early radiotherapy of 54 Gy in fractions of 1·8 Gy or deferred radiotherapy until the time of progression (control group). Patients with low-grade astrocytoma, oligodendroglioma, mixed oligoastrocytoma, and incompletely resected pilocytic astrocytoma, with a WHO performance status 0–2 were eligible. Analysis was by intention to treat, and primary endpoints were overall and progression-free survival.

Findings

157 patients were assigned early radiotherapy, and 157 control. Median progression-free survival was 5·3 years in the early radiotherapy group and 3·4 years in the control group (hazard ratio 0·59, 95% CI 0·45–0·77; p<0·0001). However, overall survival was similar between groups: median survival in the radiotherapy group was 7·4 years compared with 7·2 years in the control group (hazard ratio 0·97, 95% CI 0·71–1·34; p=0·872). In the control group, 65% of patients received radiotherapy at progression. At 1 year, seizures were better controlled in the early radiotherapy group.

Interpretation

Early radiotherapy after surgery lengthens the period without progression but does not affect overall survival. Because quality of life was not studied, it is not known whether time to progression reflects clinical deterioration. Radiotherapy could be deferred for patients with low-grade glioma who are in a good condition, provided they are carefully monitored.

Introduction

Many aspects of treatment for low-grade glioma are controversial. No evidence-based guidelines exist for the “wait and see” policy in young patients with low-grade glioma who present with seizures only; the effectiveness of extensive resection compared with more limited surgical procedures and the use of chemotherapy is unknown. The effectiveness of radiotherapy is also unclear.

In the mid 1980s, European investigators explored the role of radiotherapy in two randomised studies. The first study (EORTC 22844)1 investigated the presence of a dose–response relation for patients with low-grade glioma who were treated with radiotherapy. Together with a similar American study,2 this study made clear that within a range of 45 to 65 Gy given in fractions of 1·8 Gy, the progression-free survival and overall survival in patients with low-grade glioma is independent of the radiation dose given. Now a radiation dose of 50–54 Gy in fractions of 1·8 Gy is the accepted treatment for low-grade glioma.

The second EORTC trial (EORTC 22845) addressed a more fundamental question. This study, activated in 1986, is the only randomised study in low-grade glioma to compare an active treatment with a conservative approach (the “wait-and-see” policy). The study assessed the efficacy of early radiotherapy versus deferred treatment (including radiotherapy) at the time of progression. An interim analysis of this study was done in 1998, which found no overall survival benefit of early radiotherapy, although it did show a small increase in progression-free survival.3 At the interim analysis which was done after a minimum follow-up duration of 14 months (median 60 months), only 30% of patients had died and 49% had progressed. We now present the long-term results of the study with a median follow-up of 93 months.

Section snippets

Patients

Before entry to the study (and during follow-up) physical and neurological assessments were done, including the WHO performance status and the Medical Research Council neurological function scale (panel). Eligibility criteria were: a) supratentorial and histologically proven low-grade astrocytoma (including incompletely resected grade I pilocytic astrocytomas), low-grade oligoastrocytoma, or low-grade oligodendroglioma according to the 1979 WHO Classification for Central Nervous System Tumours;4

Results

311 patients were randomised, of whom 303 (97%) were eligible; reasons for non-eligibility were incomplete data before entry to the study, performance status greater than 2 or older than 65 years of age, and missing follow-up data (figure 1). After follow-up for a median of 7·8 years (March 2004), 217 (70%) patients had progressed and 156 patients had died (50%). 142 (91%) patients died from a progressive brain tumour, 12 (8%) patients died from unrelated causes, and no information on the cause

Discussion

This study shows that immediate post-operative irradiation in patients with low-grade glioma increases the median progression-free survival by 2 years, without affecting overall survival. The interim analysis presented some differences in progression-free survival, but these were of little clinical significance.3 In that analysis, early radiotherapy increased 5-year progression-free survival by only 7% (from 37% to 44%). In the present analysis, the improvement in 5-year progression-free

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